B6-hIL6ST Mouse

The IL6ST gene, also known as gp130, encodes a crucial signal-transducing protein that is part of the receptor complex for a wide range of cytokines, including Interleukin-6 (IL-6), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), and oncostatin M (OSM) ^[1]. This protein is ubiquitously expressed across various cellular tissues, including but not limited to the brain, heart, thymus, spleen, kidney, lung, liver, and endometrial tissues, playing critical roles in mediating signals that regulate immune response, hematopoiesis, pain control, bone metabolism, and embryonic development. Its function involves homodimerization upon cytokine binding to initiate intracellular signaling pathways like JAK-MAPK and JAK-STAT3, thereby influencing cell proliferation, differentiation, and survival ^[2]. Dysregulation or mutations in IL6ST are associated with several diseases, notably various forms of Hyper-IgE Syndrome (HIES), particularly Hyper-IgE recurrent infection syndrome type 4 (autosomal recessive and dominant forms), as well as playing a role in conditions like rheumatoid arthritis, multiple sclerosis, Crohn's disease, inflammatory bowel disease, breast cancer, and endometriosis ^[3-4].

The B6-hIL6ST mouse is a humanized model constructed by replacing the endogenous partial extracellular domain of the mouse Il6st gene with the human IL6ST partial extracellular domain. The murine signal peptide, transmembrane, and cytoplasmic domains are preserved. B6-hIL6ST mice can be used for research into the pathogenesis of inflammatory and autoimmune diseases, as well as certain tumors, and for the screening, development, and safety evaluation of IL6ST-targeted drugs.